Tuesday, July 21, 2015

Chitotriosidase hurts chitin-makers and indicates inflammatory diseases

Five years prior to noticing a fungus eating its way across a slice of bacteria-laden agar and setting in motion a marked decline in human mortality from infections, Alexander Fleming smeared a bit of snot on an agar slice and found an enzyme capable of corroding bacterial cell walls. He named this enzyme lysozyme due to its effect on bacterial colonies (lyso- = dissolving). Lysozyme is present in tears, mucus, saliva, and human milk, providing an early line of defence against disease-causing bacterial invaders.

Chitotriosidase is one of lysozyme's coworkers, the two being produced together in the tear-making lacrimal glands above the eyes. It's an enzyme that can break apart chitin, a structural biopolymer found in various eukaryotes including fungi, protists, roundworms, insects, and crustaceans. Chitotriosidase is made by neutrophils and activated macrophages (i.e. pathogen-killing white blood cells that are part of the innate immune system), pointing to a role in the body's defence against disease-causing organisms. Supporting this, people who have a genetic mutation that causes them to make an inactive form of chitotriosidase appear to be more susceptible to infections with chitin-containing pathogens (e.g. Candida albicans and Wuchereria bancrofti).

Chitotriosidase and lysozyme are probably hanging out on your eyeball right now

One of the mutations that renders chitotriosidase inactive is common in Asian and Amerindian populations, uncommon in Europeans, and rarely occurs in West and South Africans. This suggests certain factors came into play over the course of human migration that influenced the utility of the enzyme (e.g. reduced need for protection against malaria, which is caused by certain chitin-containing Plasmodium species).

Due to the involvement of chitotriosidase-producing white blood cells in the inflammatory response and their propensity to kick it into overdrive in this setting, there tends to be more of the enzyme circulating in the bloodstream of people with inflammatory diseases. Elevated chitotriosidase activity can be used to diagnose and monitor the treatment of rare lipid storage diseases (e.g. Gaucher disease), often via the use of dried blood spot testing. Relatively high concentrations of the enzyme have also been found in folks with multiple sclerosis, atherosclerosis, and interstitial lung diseases. It's thought that chitotriosidase actively participates in the progression of some inflammatory diseases (e.g. by driving fibrosis of the liver and lungs), but it may have a protective function as well (e.g. reducing lung injury due to dust inhalation).


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